The role of IL-13 in IgE synthesis by allergic asthma patients.
IgE antibodies play a crucial role in allergic type I reactions. Only IL-4 and IL-13 are able to induce an immunoglobulin isotype switch to IgE in B cells. A major question is to what extent these cytokines contribute to the production of IgE in allergic patients. To address this question we used an in vitro culture system in which the production of IgE is dependent on endogenously produced IL-4 and IL-13. In cultures of purified T and B cells from allergic asthma patients and non-atopic controls, T cells were polyclonally stimulated to obtain IL-4, IL-13 and subsequently IgE secretion. The absolute amount of IgE produced was not significantly different between patients and controls. When neutralizing IL-4 antibodies were included during culture, the production of IgE was dramatically inhibited in both patients and controls (production of IgE was reduced to 12%). However, neutralization of IL-13 led to a significantly stronger inhibition of IgE production in the patient group: production of IgE was reduced to 23 +/- 3% versus 50 +/- 10% in the control group. Corresponding with these results, we also observed a higher production of IL-13 by the patients, while the production of IL-4 was not significantly different. A more detailed analysis of the production of IL-13 revealed that patients' T cells were less sensitive to a negative signal controlling IL-13 production. Our results indicate that, at least in vitro, IgE production in allergic asthma patients is more dependent on IL-13 than in non-atopics, due to enhanced IL-13 production and to enhanced IgE production in response to IL-13.
Van der Pouw Kraan
T C
TC
Department of Auto-Immune Diseases, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Van der Zee
J S
JS
Boeije
L C
LC
De Groot
E R
ER
Stapel
S O
SO
Aarden
L A
LA
D000328:Adult; D001249:Asthma / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D018793:Interleukin-13 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
D018793:Interleukin-13; D007073:Immunoglobulin E